With the development of transgenic mouse technology in the early 1980s, it became increasingly clear that the ability to introduce foreign genes into the germline of mice and target the expression of these genes to particular transgenic tissues would revolutionize developmental and molecular biology. In particular, the ability to target growth or tumor promoting factors to transgenic tissues has provided tremendous potential for the development of animal models for hyperproliferative diseases and tumorigenesis. Such technology is a fundamental prerequisite for our understanding of the molecular mechanisms leading to specific types of tumors and for the establishment of new and improved therapeutic agents for the treatment of these diseases. A powerful use of transgenic mouse technology is in immunology. the UCCRC has an extremely strong group of molecular immunologists who are currently utilizing transgenic mouse technology to study (1) the molecular basis for somatic hypermutation during B-cell development (Ursula Storb), (2) the role of methylation in differentiation-specific gene expression (Ursula Storb), (3) the role of transcriptional regulatory genes in B-cell development (Harinder Singh), (4) the role of Hassall's corpuscles in thymic development (Jeffrey Bluestone and Elaine Fuchs) and (5) T-cell development in general (Jeffrey Bluestone). Another example of the value of this technology is in understanding hyperproliferative diseases of stratified squamous epithelium. Dr. Elaine Fuchs has identified DNA sequences necessary for targeting expression of genes to the mitotically active cells of squamous epithelium and has shown that these promoter/enhancers can be used to target keratinocyte-specific expression of genes encoding growth factors such as TGF-alpha. Clearly, the potential uses of transgenic mouse technology for cancer research are wide ranging, and, in the past several years, the interest in this technology by UCCRC members has escalated exponentially. The expense involved in the technology necessitates a shared facility. It requires expensive equipment and considerable technical expertise. Finally, the cost of a mouse colony with pseudopregnant females, pregnant females and vasectomized males, is exorbitant. Through the use of a shared and partially subsidized facility, a large number of faculty in the UCCRC will be able to take advantage of this most important technology.